Vitamin E is a fat-soluble vitamin necessary in the diet of many species for normal reproduction, normal development of muscles, normal resistance of erythrocytes to hemolysis, and various other biochemical functions. The most widely accepted function of vitamin E is an an antioxidant, protecting polyunsaturated fatty acids in membranes and other cellular structures from attack by free radicals. Vitamin E occurs in cereals (especially wheat germ and corn), sunflower seed, rapeseed, soybean oil, alfalfa, lettuce, egg yolk, and beef liver, and consists primarily of three molecular species of tocol derivatives, the alpha-, beta- and gamma- tocopherols, of which alpha-tocopherol is most important because it has the widest distribution and greatest biological activity.
Other tocopherols have been found in nature, including gamma-, eta-, zeta.sub.2, zeta.sub.1 - and epsilon-tocopherol. The last two species, which occur in cereal grains, have unsaturated hydrocarbon tails and have been recently called tocotrienols (denoted alpha- and beta-tocotrienol, respectively) because each has three double bonds in the side chain, and this nomenclature distinguishes them from tocopherols bearing saturated tails. Gamma-tocopherol is claimed to be the most potent antioxidant of any tocopherol species (The Merck Index, 11th ed., 1989, entries 9417 to 9423 and 9931), but activity appears to be dependent on the system used for measurement. Thus, in the in vitro systems of Burton, G. W., et al., J. Am. Chem. Soc. 107:7073-7065 (1985), for example, alpha-tocopherol was the most powerful antioxidant.
The antioxidant function of vitamin E per se is localized in the chromanol nucleus, where the phenolic hydroxy group donates a hydrogen atom to quench lipid radicals ibid., and Serbinova, E., et al., Free Radical Biology & Med., 10:263-275 (1991)). The antioxidant potency of vitamin E is determined by the efficiency of the tocopherol in scavenging radicals and by the reactivity of the chromanoxyl radical formed in further propagation of lipid peroxidation or in the regeneration of the tocopherol due to interaction of the chromanoxyl radical with reductants; the latter does not propagate lipid peroxidation.
In homogenous solutions, the rate constants of the reaction between the chromanol nucleus and radicals do not depend upon the length or unsaturation of the tocopherol hydrocarbon tails, but mainly depend on the number of methyl groups in the benzene ring of the chromanol nucleus (Burton, G. W., et al., cited above). Similarly, the reactivity of the chromanoxyl radical is mainly determined by hindering effects of the methyl groups.
The situation is more complex in heterogenous membrane systems, however, where vitamin E appears to owe its antioxidant potency not solely to the chemistry of the tocopherol molecule but also to its mobility and accessibility within the membrane (Serbinova, cited above). In some systems, tocotrienols appear to have higher antioxidant activity (ibid.). However, in others, direct comparisons of antioxidant efficiency of tocopherols having saturated tails with tocotrienols did not demonstrate decisive differences in the activities of these two forms of vitamin E (ibid. and Nakano, M., et al., Biochim. Biophys. Acta 619:274-286 (1980)).
The antioxidant activity of tocotrienol prevents free radical damage to cells and cell components. Free radical damage is most evident in cellular membranes because of the density of the molecular structure of the membranes. It is currently hypothesized that cell membrane aging leads to all of the various cellular changes seen in aging, such as decreased RNA production, decreased protein production, and faulty enzyme action.
Inflammation in skin is mediated by several active chemicals and metabolites of arachidonic acid. Arachidonic acid is oxidized by cyclo-oxygenase and lipoxygenase to active metabolites such as the leukotrienes and 5- and 12- hydroxyeicosatetraenoic acid (HETES). Within the arachidonic acid cascade, many free radicals are generated, which both perpetuate and magnify the inflammatory cascade, resulting in skin damage and manifested clinically as erythema.
Early suggestions for dealing with erythema and aging effects in skin were predominantly aimed at lubrications and emollients through use of topical compositions containing soothing agents, e.g., as exemplified by commercial hand lotion products and the like. More recently, attention has been directed to agents which address the underlying processes involved in skin damage, such as the free radical generation processes. In this regard, investigations have been made with respect to the antioxidants vitamin E and vitamin C to quench free radicals on the surface of the skin and to protect lipid membranes intracellularly (Wilson, R., Drug and Cosmetic Industry, 32-34, 38, and 68, August 1992).
Damage to hair, particularly damage caused by excessive exposure to sunlight or harsh chemicals, is also mediated in part by oxidation of keratin. Traditional remedies typically add oil in a conditioner or shampoo to ameloriate the hair's dryness and brittleness.
It would be desirable to have alternative topical compositions for anti-inflammatory and anti-aging effects observed in skin, particularly compositions that are efficient in free radical scavenging in membranes. It would also be desirable to have hair treatments that treat the actual cause of hair damage, rather than merely assuage its effects.